We have recently identified and partially purified a novel peptidase from human postmortem cerebral cortex which degrades somatostatin, luteinizing hormone-releasing hormone and probably other neuropeptides. We propose in this application to: 1) Purify to homogeneity this novel neuropeptide-degrading enzyme from postmortem human cerebral cortex. 2) Characterize this enzyme in terms of its molecular weight, pH optimum, Michaelis-Menton kinetics, behavior in the presence of enzyme inhibitors and activators, bond and substrate specificities, and stability in postmortem tissue. 3) The regional distribution and subcellular localization of the enzyme will be determined as a further step toward defining its biological role. Our purification procedures will include ion-exchange and gel filtration chromatography as well as affinity and covalent chromatography. Other aspects of the study will employ SDS-polyacrylamide gel electrophoresis, radioimmunoassay for somatostatin, and conventional techniques for peptide analysis. Our long-term objectives are to elucidate the biological role of this enzyme in normal brain function and to determine its involvement in neuropsychiatric disorders.